UMIN-CTR 臨床試験登録情報の閲覧

一般向け試験名/Public title

日本語
進行、局所進行、再発NSCLCに対するICI治療のRCTでのHR_PFSがHR_OSを代用できるか。

英語
HR of PFS as surrogate endpoints for HR of OS in RCTs of systemic immuno-therapies for advanced, locally advanced, and relapsed NSCLC

一般向け試験名略称/Acronym

日本語
進行、局所進行、再発NSCLCに対するICI治療のRCTでのHR_PFSがHR_OSを代用できるか。

英語
HR of PFS as surrogate endpoints for HR of OS in RCTs of systemic immuno-therapies for advanced, locally advanced, and relapsed NSCLC

科学的試験名/Scientific Title

日本語
進行、局所進行、再発NSCLCに対するICI治療のRCTでのHR_PFSがHR_OSを代用できるか。

英語
HR of PFS as surrogate endpoints for HR of OS in RCTs of systemic immuno-therapies for advanced, locally advanced, and relapsed NSCLC

科学的試験名略称/Scientific Title:Acronym

日本語
進行、局所進行、再発NSCLCに対するICI治療のRCTでのHR_PFSがHR_OSを代用できるか。

英語
HR of PFS as surrogate endpoints for HR of OS in RCTs of systemic immuno-therapies for advanced, locally advanced, and relapsed NSCLC

試験実施地域/Region

日本/Japan

対象疾患名/Condition

日本語
進行、局所進行、再発NSCLC

英語
advanced, locally advanced, and relapsed NSCLC

疾患区分1/Classification by specialty

呼吸器内科学/Pneumology

疾患区分2/Classification by malignancy

悪性腫瘍/Malignancy

ゲノム情報の取扱い/Genomic information

いいえ/NO

目的1/Narrative objectives1

日本語
英文参照

英語
Although OS is universally recognized as the gold-standard endpoint in oncology clinical trials due to its direct clinical benefit to patients and objective, bias-free measurement, evaluating it has become ironically complex. Thanks to therapeutic breakthroughs by ICIs, the survival of patients with inoperable NSCLC spans several years. Consequently, executing randomized controlled trials (RCTs) with mature OS as the primary endpoint requires protracted follow-up periods, making them increasingly impractical. To overcome this logistical barrier, intermediate metrics such as progression-free survival (PFS) have gained widespread adoption as a primary endpoint. Most of published systematic review did not show very good relationship between HRs of PFS and OS, partially due to pseudo-progression. Another issue is underestimating the surrogacy due to statistical phenomenon, insufficient correlation by restricted range. Recent ICI trials showed highly favorable HRs of PFS and OS because of excellent therapeutic effect by ICI and because of medical tradition assigning standard treatment to the reference arm and novel treatment to the experiment arm. In this study, we conducted a trial-level systematic review to assess the formal validity of HR of PFS as a surrogate endpoint for HR of OS in RCTs with ICI for advanced, locally advanced, and relapsed NSCLC.

目的2/Basic objectives2

その他/Others

目的2 -その他詳細/Basic objectives -Others

日本語
英文参照

英語
Most of published systematic review did not show very good relationship between HRs of PFS and OS, partially due to pseudo-progression. Another issue is underestimating the surrogacy due to statistical phenomenon, insufficient correlation by restricted range. Recent ICI trials showed highly favorable HRs of PFS and OS because of excellent therapeutic effect by ICI and because of medical tradition assigning standard treatment to the reference arm and novel treatment to the experiment arm. In this study, we conducted a trial-level systematic review to assess the formal validity of HR of PFS as a surrogate endpoint for HR of OS in RCTs with ICI for advanced, locally advanced, and relapsed NSCLC.

試験の性質1/Trial characteristics_1

試験の性質2/Trial characteristics_2

試験のフェーズ/Developmental phase

主要アウトカム評価項目/Primary outcomes

日本語
英文参照

英語
The surrogacy of HR of PFS for HR of OS.
To eliminate potential bias arising from arbitrary label-/arm-assignment, an exhaustive label-assignment method is developed. For N RCTs, all 2^N possible label-assignment patterns are evaluated. STE, correlation coefficient, and P-values are determined as the median values across all 2^N sign-permutations.
Surrogacy is evaluated using the weighted Peason's correlation coefficient (r). According to the generic inverse variance method, the weight assigned to each study is determined by the inverse variance of the natural log HR of survival, where the variance is the squared standard error. The correlation is interpreted as follows: no correlation (|r| < 0.2), weak (0.2 < |r| < 0.4), moderate (0.4 < |r| < 0.6), strong (0.6 < |r| < 0.8), very strong (0.8 < |r| < 0.9), or excellent (0.9 < |r|).
Statistical significance is determined by a Z-statistic by dividing the random-effects meta-regression slope coefficient by its standard error, which inherently incorporates both within-trial sampling variances and between-trial heterogeneity (tau^2). The corresponding P-value is derived from this Z-statistic.
A bivariate random-effects meta-analytic model is utilized to jointly model treatment effects on both endpoints and to estimate their variance-covariance structure. From this joint framework, the trial-level surrogate regression line and its 95% prediction interval (PI) are derived. The Surrogate threshold effect (STE) is defined as the threshold where this 95% PI crosses the line of no effect (HR = 1.0). This structural model-based approach is prioritized over ordinary univariate mixed-effects meta-regression to ensure a more robust estimation of the surrogacy relationship.

副次アウトカム評価項目/Key secondary outcomes

日本語

英語

試験の種類/Study type

その他・メタアナリシス等/Others,meta-analysis etc

基本デザイン/Basic design

ランダム化/Randomization

ランダム化の単位/Randomization unit

ブラインド化/Blinding

コントロール/Control

層別化/Stratification

動的割付/Dynamic allocation

試験実施施設の考慮/Institution consideration

ブロック化/Blocking

割付コードを知る方法/Concealment

群数/No. of arms

介入の目的/Purpose of intervention

介入の種類/Type of intervention

介入1/Interventions/Control_1

日本語

英語

介入2/Interventions/Control_2

日本語

英語

介入3/Interventions/Control_3

日本語

英語

介入4/Interventions/Control_4

日本語

英語

介入5/Interventions/Control_5

日本語

英語

介入6/Interventions/Control_6

日本語

英語

介入7/Interventions/Control_7

日本語

英語

介入8/Interventions/Control_8

日本語

英語

介入9/Interventions/Control_9

日本語

英語

介入10/Interventions/Control_10

日本語

英語

年齢（下限）/Age-lower limit

適用なし/Not applicable

年齢（上限）/Age-upper limit

適用なし/Not applicable

性別/Gender

男女両方/Male and Female

選択基準/Key inclusion criteria

日本語
英文参照

英語
Study selection
Articles written in English that present a randomised controlled trial (RCT) evaluating systemic immune-therapy for advanced, locally advanced, and relapsed NSCLC are eligible for inclusion. Conference abstracts are not accepted.

Patients
Patients with operable NSCLC are evaluated, irrespective of pathological subtype or driver mutation, provided they are considered candidates for systemic immune-therapy by the original study authors.

Treatment
This study focuses on ICI-based systemic immuno-therapy such as ICI monotherapy, dual ICI therapy, and chemoimmunotherapy.
Absence or presence of previous systemic therapy is not considered. However, subgroup analysis focusing on first-line treatment and on second- or later-line treatment are expected.

除外基準/Key exclusion criteria

日本語
英文参照

英語
Conference abstracts are not accepted.

Systematic therapy without ICI is not allowed. Multimodal treatment combined with radiotherapy is excluded. Studies utilising regimens containing obsolete cytotoxic agents, such as mitomycin C and vindesine, are also excluded as they do not represent current standard-of-care.

目標参加者数/Target sample size

責任研究者/Name of lead principal investigator

日本語

名	信之
ミドルネーム
姓	堀田

英語

名	Nobuyuki
ミドルネーム
姓	Horita

所属組織/Organization

日本語
横浜市立大学附属病院

英語
Yokohama City University Hospital

所属部署/Division name

日本語
化学療法センター

英語
Chemotherapy Center

郵便番号/Zip code

236-0004

住所/Address

日本語
横浜市金沢区福浦３－９

英語
3-9, Fukuura, Kanazawa, Yokohama, Japan

電話/TEL

045-787-2800

Email/Email

horitano@yokohama-cu.ac.jp

試験問い合わせ窓口担当者/Name of contact person

日本語

名	信之
ミドルネーム
姓	堀田

英語

名	Nobuyuki
ミドルネーム
姓	Horita

組織名/Organization

日本語
横浜市立大学附属病院

英語
Yokohama City University Hospital

部署名/Division name

日本語
化学療法センター

英語
Chemotherapy Center

郵便番号/Zip code

236-0004

住所/Address

日本語
横浜市金沢区福浦３－９

英語
3-9, Fukuura, Kanazawa, Yokohama, Japan

電話/TEL

045-787-2800

試験のホームページURL/Homepage URL

Email/Email

horitano@yokohama-cu.ac.jp

機関名/Institute

日本語
その他

英語
Yokohama City University Hospital

機関名/Institute
（機関選択不可の場合）

日本語
横浜市立大学附属病院

部署名/Department

日本語

個人名/Personal name

日本語

英語

機関名/Organization

日本語
無し

英語
Yokohama City University Hospital

機関名/Organization
（機関選択不可の場合）

日本語
横浜市立大学附属病院

組織名/Division

日本語

組織の区分/Category of Funding Organization

その他/Other

研究費拠出国/Nationality of Funding Organization

日本語

英語

共同実施組織/Co-sponsor

日本語

英語

その他の研究費提供組織/Name of secondary funder(s)

日本語

英語

組織名/Organization

日本語
横浜市立大学附属病院

英語
Yokohama City University Hospital

住所/Address

日本語
横浜市金沢区福浦３－９

英語
3-9, Fukuura, Kanazawa, Yokohama, Japan

電話/Tel

045-787-2800

Email/Email

horitano@yokohama-cu.ac.jp

他機関から発行された試験ID/Secondary IDs

いいえ/NO

試験ID1/Study ID_1

ID発行機関1/Org. issuing International ID_1

日本語

英語

試験ID2/Study ID_2

ID発行機関2/Org. issuing International ID_2

日本語

英語

治験届/IND to MHLW

試験実施施設名称/Institutions

一般公開日（本登録希望日）/Date of disclosure of the study information

2026

年

05

月

30

日

プロトコル掲載URL/URL releasing protocol

試験結果の公開状況/Publication of results

未公表/Unpublished

結果掲載URL/URL related to results and publications

組み入れ参加者数/Number of participants that the trial has enrolled

主な結果/Results

日本語

英語

主な結果入力日/Results date posted

結果掲載遅延/Results Delayed

結果遅延理由/Results Delay Reason

日本語

英語

最初の試験結果の出版日/Date of the first journal publication of results

参加者背景/Baseline Characteristics

日本語

英語

参加者の流れ/Participant flow

日本語

英語

有害事象/Adverse events

日本語

英語

評価項目/Outcome measures

日本語

英語

個別症例データ共有計画/Plan to share IPD

日本語

英語

個別症例データ共有計画の詳細/IPD sharing Plan description

日本語

英語

試験進捗状況/Recruitment status

開始前/Preinitiation

プロトコル確定日/Date of protocol fixation

2026

年

05

月

29

日

倫理委員会による承認日/Date of IRB

登録・組入れ開始（予定）日/Anticipated trial start date

2026

年

05

月

29

日

フォロー終了(予定)日/Last follow-up date

2027

年

12

月

31

日

入力終了(予定)日/Date of closure to data entry

データ固定（予定）日/Date trial data considered complete

解析終了(予定)日/Date analysis concluded

その他関連情報/Other related information

日本語
英文参照

英語
S. Yamamoto and N. Horita extract data regarding study characteristics, hazard ratios (HR) for survival data with 95% confidence intervals (CI), and risk-of-bias items. Extracted data are cross-verified. For studies reporting multiple populations, the primary endpoint population or the population with the larger sample size is selected. Priority is given to the protocol-specific primary endpoint; however, updated data are used for overall survival (OS) if the primary article's data are immature.

登録日時/Registered date

2026

年

05

月

30

日

最終更新日/Last modified on

2026

年

05

月

30

日

閲覧ページへのリンク/Link to view the page

日本語
https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000070662

英語
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000070662